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Preclinical data indicated that antagonists of group I mGlu receptors, particularly antagonists of mGlu5 receptors, produced both anxiolytic-like and antidepressant-like effects. Clinical data also demonstrated that mGlu5 receptor antagonist, fenobam, was an active anxiolytic drug. The anxiolytic effects exerted by mGlu5 receptor antagonists are profound, comparable to or stronger than those of benzodiazepines. Among all mGlu receptor ligands, group II mGlu receptor agonists seem to be drugs with promising therapeutic potential and good safety profi le. Animal studies showed anxiolytic-like effects of group II mGlu receptor agonists. Currently, group II mGlu receptor agonists are in phase III clinical trials for potential treatment of anxiety disorders. On the other hand, data have been accumulated indicating that antagonists of group II mGlu receptors have an antidepressant potential. Group III mGlu receptor ligands represent the least investigated group of mGlu receptors. The preclinical data, however, indicate that a selective agonist of mGlu4 and Glu8 receptors- ACPT-I produced anxiolytic but not antidepressant effects after peripheral administration, while the selective positive allosteric modulator of Glu7 receptors, AMN082 produced both anxiolytic and antidepressantlike. The data show that the effects of group III mGlu receptor ligands may differ dependently of their receptor subtype specifi city
Background: The metabotropic glutamate receptors play important neuromodulatory role throughout the brain. Intervention in glutamatergic neurotransmission through group III of mGluRs has been pursued for the treatment of many neurological and psychiatric disorders such as anxiety, schizophrenia, epilepsy, Parkinson disease, addiction. Aim: Identification of novel chemical scaffolds possessing group III of mGluRs positive allosteric modulation (PAM) activity. Methods: The screening study and activity of potential PAM was determined using forskolin-induced cAMP production, in HEK-293 T-REx cell lines stably expressing mGluRs (HTRF cAMP detection kit, Cisbio). Results: We have identified chemical scaffolds possessing mGluRs potential PAM activity. Those compounds alone and in the presence of L-Glutamine decreased the forskolin-induced cAMP production in HEK-293 T-REx mGluRs cells. Conclusions: It have been identified novel chemical scaffolds with mGluRs potential positive allosteric modulator activity. Acknowledgments This study is supported by project UDAPOIG.01.03.010-12-100/08-00 co-financed by European Union from the European Fund of Regional Development.
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